{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:36:13Z","timestamp":1792668973545,"version":"4.5.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,3,14]]},"abstract":"<jats:p>\n                    Mosquitoes (\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    ) were genetically modified to exhibit impaired vector competence for dengue type 2 viruses (DENV-2). We exploited the natural antiviral RNA interference (RNAi) pathway in the mosquito midgut by constructing an effector gene that expresses an inverted-repeat (IR) RNA derived from the premembrane protein coding region of the DENV-2 RNA genome. The\n                    <jats:italic>A. aegypti carboxypeptidase A<\/jats:italic>\n                    promoter was used to express the IR RNA in midgut epithelial cells after ingestion of a bloodmeal. The promoter and effector gene were inserted into the genome of a white-eye Puerto Rico Rexville D (Higgs\u2019 white eye) strain by using the nonautonomous\n                    <jats:italic>mariner MosI<\/jats:italic>\n                    transformation system. A transgenic family, Carb77, expressed IR RNA in the midgut after a bloodmeal. Carb77 mosquitoes ingesting an artificial bloodmeal containing DENV-2 exhibited marked reduction of viral envelope antigen in midguts and salivary glands after infection. DENV-2 titration of individual mosquitoes showed that most Carb77 mosquitoes poorly supported virus replication. Transmission\n                    <jats:italic>in vitro<\/jats:italic>\n                    of virus from the Carb77 line was significantly diminished when compared to control mosquitoes. The presence of DENV-2-derived siRNAs in RNA extracts from midguts of Carb77 and the loss of the resistance phenotype when the RNAi pathway was interrupted proved that DENV-2 resistance was caused by a RNAi response. Engineering of transgenic\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    that show a high level of resistance against DENV-2 provides a powerful tool for developing population replacement strategies to control transmission of dengue viruses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0600479103","type":"journal-article","created":{"date-parts":[[2006,3,6]],"date-time":"2006-03-06T20:34:02Z","timestamp":1141677242000},"page":"4198-4203","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":357,"title":["Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified\n                    <i>Aedes aegypti<\/i>"],"prefix":"10.1073","volume":"103","author":[{"given":"Alexander W. E.","family":"Franz","sequence":"first","affiliation":[{"name":"*Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Sanchez-Vargas","sequence":"additional","affiliation":[{"name":"*Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zach N.","family":"Adelman","sequence":"additional","affiliation":[{"name":"Department of Entomology, 320 Price Hall, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol D.","family":"Blair","sequence":"additional","affiliation":[{"name":"*Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Beaty","sequence":"additional","affiliation":[{"name":"*Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A.","family":"James","sequence":"additional","affiliation":[{"name":"Departments of Molecular Biology and Biochemistry and"},{"name":"Microbiology and Molecular Genetics, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken E.","family":"Olson","sequence":"additional","affiliation":[{"name":"*Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,3,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0403.980326"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1105.050195"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.651"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.11.040"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2395"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0965-1748(02)00096-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/417452a"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.11.004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781420042030.ch10"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5263.884"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/78531"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/72850"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502815102"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12925-12933.2002"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.01.017"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/157.2.471"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004270000111"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.20.10895"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2583.2000.00159.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/156.2.687"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1998.59.965"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80620-0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.862301"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2583.2001.00267.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.14147"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301717200"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-2-53"},{"key":"e_1_3_3_28_2","first-page":"127","volume":"6","author":"Sontheimer E. 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